Gothelf, K. V.; Thomsen, I.; Jørgensen, K. A.
J. Am. Chem. Soc. 1996, 118, 59–64, doi: 10.1021/ja952726e
AARHUS UNIV,DEPT CHEM,DK-8000 AARHUS,DENMARK
A highly diastereo- and enantioselective metal-catalyzed 1,3-dipolar cycloaddition reaction of 3-((E)-2′-alkenoyl)-1,3-oxazolidin-2-ones with nitrones has been developed. A series of TiX(2)-TADDDLate catalysts are investigated for their effects on the rate and diastereo- and enantioselectivities in the 1,3-dipolar cycloaddition reaction of alkenes with nitrones. The TiCl2-TADDOLate catalysts are known to catalyze the 1,3-dipolar cycloaddition reaction of alkenes with nitrones, giving primarily the exo-isomer of the isoxazolidines with an optical purity of up to 60% ee. If the chloride atoms of the catalyst are substituted with more bulky Ligands, such as the tosylato ligand, the endo-isomer is obtained with a diastereoselectivity of >90%. The synthetic aspects of this new method are presented by a series of reactions in which diastereoselectivities of >90% are generally obtained and, most remarkably, enantioselectivities of >90% are frequently obtained. The diastereo- and enantioselectivities of the reaction of the alkenes with nitrones can be accounted for by a transition state model directly derived from a TiCl2-TADDOLate-3-cinnamoyloxazolidinone intermediate which has recently been isolated and characterized.